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Differential activation profiles of Crimean-Congo hemorrhagic fever virus versus Dugbe virus infected antigen presenting cells

¹ Armed Forces Biomedical Research Institute (IRBA), Emile Parde, Grenoble, France;
² Emerging Pathogens Laboratory, Fondation Merieux, IFR128 BioSciences Lyon-Gerland, Lyon, France;
³ INSERM Jean Merieux, Lyon, France;
⁴ Institut Pasteur, Unite de Genetique Moleculaire des Bunyavirus, Paris, France

⁵ E-mail: mbouloy{at}pasteur.fr

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus member of the Bunyaviridae family and the Nairovirus genus. To better elucidate the pathogenesis of CCHFV, we analyzed the host innate immune response induced in antigen presenting cells (APC) infected in vitro by CCHFV. Monocyte-derived dendritic cells (DCs) and macrophages (MPs) both were shown to be permissive to CCHFV and to replicate the virus as monitored by genomic and anti-genomic strand quantification. Virus replication was however controlled, corroborating an efficient IFN- induced response. The up-regulation of CD-83, CD-86 indicated that CCHFV induced a partial maturation of DCs which were shown also to activate the secretion of IL-6 and IL-8 but no TNF- . On the other hand, in MPs, CCHFV infection elicited a high Il-6 and TNF- response and moderate chemokine response. Nevertheless, when we compared the response of these APCs after infection with Dugbe virus (DUGV), a mild pathogenic virus genetically close to CCHFV, we found that, in spite of some similarities, DUGV induced a higher cytokine/chemokine response in MPs. These results suggest that CCHFV was able to selectively inhibit the activation of the inflammatory mediators in the in vitro infection and that these differences could be relevant in pathogenesis.

Received 6 August 2009; accepted 1 October 2009.