How to cite this article: Vet. Res. (2010) 41:07
DOI: 10.1051/vetres/2009055

Acute induction of cell death-related IFN stimulated genes (ISG) differentiates highly from moderately virulent CSFV strains

Patricia Renson¹, Yannick Blanchard², Mireille Le Dimna¹, Hélène Felix², Roland Cariolet³, André Jestin² and Marie-Frédérique Le Potier<sup>1

1</sup>  Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Unité Virologie et Immunologie Porcines, BP 53, 22440 Ploufragan, France
²  Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Unité Génétique Virale et Biosécurité, BP 53, 22440 Ploufragan, France
³  Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Service Production de Porcs Assainis et d'Expérimentations, BP 53, 22440 Ploufragan, France

Received 4 June 2009; accepted 24 September 2009; published online 01 October 2009

Abstract - Classical swine fever (CSF) severity is dependent on the virulence of the CSF virus (CSFV) strain. The earliest event detected following CSFV infection is a decrease in lymphocytes number. With some CSFV strains this leads to lymphopenia, the severity varying according to strain virulence. This lymphocyte depletion is attributed to an induction of apoptosis in non-infected bystander cells. We collected peripheral blood mononuclear cells (PBMC) before and during 3 days post-infection with either a highly or moderately virulent CSFV strain and subjected them to comparative microarray analysis to decipher the transcriptomic modulations induced in these cells in relation to strain virulence. The results revealed that the main difference between strains resided in the kinetics of host response to the infection: strong and immediate with the highly virulent strain, progressive and delayed with the moderately virulent one. Also although cell death/apoptosis-related IFN stimulated genes (ISG) were strongly up-regulated by both strains, significant differences in their regulation were apparent from the observed differences in onset and extent of lymphopenia induced by the two strains. Furthermore, the death receptors apoptotic pathways (TRAILDR4, FASL-FAS and TNFa-TNFR1) were also differently regulated. Our results suggest that CSFV strains might exacerbate the interferon alpha response, leading to bystander killing of lymphocytes and lymphopenia, the severity of which might be due to the host's loss of control of IFN production and downstream effectors regulation.

Key words: classical swine fever virus / virulence / bystander apoptosis / type I interferon / microarray

Corresponding author: y.blanchard@afssa.fr mf.lepotier@afssa.fr

© INRA, EDP Sciences 2009