JVI Accepts, published online ahead of print on 24 June 2009

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J. Virol. doi:10.1128/JVI.00626-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

BLUETONGUE VIRUS TARGETS CONVENTIONAL DENDRITIC CELLS IN SKIN LYMPH

Behzad Hemati, Vanessa Contreras, Céline Urien, Michel Bonneau, Haru-Hisa Takamatsu, Peter Mertens, Emmanuel Bréard, Corinne Sailleau, Stéphan Zientara, and Isabelle Schwartz-Cornil

Virologie et Immunologie Moléculaires, UR892 INRA, Domaine de Vilvert, 78352 Jouy-en-Josas Cedex, France; Centre de Recherche en Imagerie Interventionnelle, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78350 Jouy-en-josas, France; Department of Immunology, Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK; Arbovirus Molecular Research Group, Arthropod Transmitted Diseases Programme, Institute for Animal Health, Ash Road, Pirbright, Woking, Surrey, GU24 0NF, UK; UMR 1161 Afssa/INRA/ENVA, 23 Avenue du Général de Gaulle, 94703 Maisons-Alfort, France

Bluetongue virus (BTV) is the etiological agent of ‘bluetongue’, a hemorrhagic disease of ruminants (particularly sheep), which causes important economic losses around the world. BTV is transmitted primarily via the bites of infected midges, which inject the virus into the ruminant's skin during ‘blood feeding’. The virus initially replicates in the draining lymph node, then disseminates to secondary organs where it induces oedema, hemorrhages and necrosis.

In this study, we show that ovine conventional dendritic cells (cDCs) are primary targets of BTV that contribute to the primary dissemination of BTV from the skin to draining lymph nodes. Lymph cDCs support BTV RNA and protein synthesis, as well as production of infectious virus belonging to several different BTV serotypes, regardless of their level of attenuation. Afferent lymph cell subsets, other than cDCs, showed only marginal levels of BTV protein expression. BTV infection provoked a massive recruitment of cDC cells to the sheep skin and afferent lymph, providing cellular targets for infection. Although BTV productively infects cDCs, no negative impact on their physiology was detected. Indeed, BTV infection and protein expression in cDCs enhanced their survival rate. Several serotypes of BTV stimulated the surface expression of the CD80 and CD86 costimulatory molecules on cDCs as well as the mRNA synthesis of cytokines involved in inflammation and immunity, i.e. IL12, IL1 and IL6. BTV-infected cDCs stimulated antigen-specific CD4 and CD8 proliferation as well as IFN production.

BTV initially targets cDCs, while preserving their functional properties, reflecting optimal adaptation of the virus to its host cells for its first spread.