Pathway analysis in blood cells of pigs infected with classical swine fever virus: comparison of pigs that develop a chronic form of infection or recover.
Infection of pigs with CSFV can lead to either acute disease, resulting in death or recovery, or chronic disease. The mechanisms by which CSFV manipulates the pig's first line of defence to establish a chronic infection are poorly understood. Therefore, pigs were infected with moderately virulent CSFV, and whole blood was collected on a regular basis during a period of 18 days. Using whole-genome microarrays, time-dependent changes in gene expression were recorded in blood cells of chronically diseased pigs and pigs that recovered. Bioinformatics analysis of regulated genes indicated that different immunological pathways were regulated in chronically diseased pigs compared to recovered pigs. In recovered pigs, antiviral defence mechanisms were rapidly activated, whereas in chronically diseased pigs, several genes with the potential to inhibit NF-κB- and IRF3/7-mediated transcription of type I interferons were up-regulated. Compared to recovered pigs, chronically diseased pigs failed to activate NK or cytotoxic T-cell pathways, and they showed decreased gene activity in antigen-presenting monocytes/macrophages. Remarkably, in chronically diseased pigs, genes related to the human autoimmune disease systemic lupus erythematosus (SLE) were up-regulated during the whole period of 18 days. CSFV pathology in kidney and skin resembles that of SLE. Furthermore, enzymes involved in the degradation of 1,25-dihydroxyvitamin D3 and of tryptophan to kynurenines were expressed at different levels in chronically diseased and recovered pigs. Both of these chemical processes may affect the functions of T helper/regulatory cells that are crucial for tempering the inflammatory response after a viral infection.
Livestock Research of Wageningen University and Research Centre, P.O. Box 65, 8200 AB, Lelystad, The Netherlands. marcel.hulst@wur.nl
Marcel
M
Hulst
Willie
W
Loeffen
Eefke
E
Weesendorp
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001773:Blood Cells / Q000378:metabolism* / Q000821:virology*; D002908:Chronic Disease; D006691:Classical Swine Fever / Q000276:immunology* / Q000473:pathology*; D006692:Classical Swine Fever Virus / Q000276:immunology* / Q000472:pathogenicity*; D019295:Computational Biology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007694:Killer Cells, Natural / Q000276:immunology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D046228:Microarray Analysis; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors