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Involvement of the skin during bluetongue virus infection and replication in the ruminant host

Karin E Darpel1*, Paul Monaghan13, Jennifer Simpson14, Simon J Anthony156, Eva Veronesi1, Harriet W Brooks2, Heather Elliott17, Joe Brownlie2, Haru-Hisa Takamatsu1, Philip S Mellor1 and Peter PC Mertens1

Author Affiliations

1 Vector-borne Viral Disease programme, Institute for Animal Health, Ash Road, Pirbright GU240NF, United Kingdom

2 Department of Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, United Kingdom

3 Current Address: Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia

4 Current Address: Histopathology, Maidstone Hospital, Hermitage Lane, Maidstone, Kent, ME16 9QQ, United Kingdom

5 Current Address: Columbia University, Center for Infection and Immunity, 722 West 168th Street, New York City, NY, USA

6 EcoHealth Alliance (formerly Wildlife Trust), 460 West 34th Street, New York City, NY, USA

7 Current Address: Department of Health, Richmond House, 79 Whitehall, London, SW1A 2NS, United Kingdom

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Veterinary Research 2012, 43:40  doi:10.1186/1297-9716-43-40

Published: 30 April 2012

Abstract

Bluetongue virus (BTV) is a double stranded (ds) RNA virus (genus Orbivirus; family Reoviridae), which is considered capable of infecting all species of domestic and wild ruminants, although clinical signs are seen mostly in sheep. BTV is arthropod-borne (“arbovirus”) and able to productively infect and replicate in many different cell types of both insects and mammalian hosts. Although the organ and cellular tropism of BTV in ruminants has been the subject of several studies, many aspects of its pathogenesis are still poorly understood, partly because of inherent problems in distinguishing between “virus replication” and “virus presence”.BTV replication and organ tropism were studied in a wide range of infected sheep tissues, by immuno-fluorescence-labeling of non-structural or structural proteins (NS2 or VP7 and core proteins, respectively) using confocal microscopy to distinguish between virus presence and replication. These results are compared to gross and microscopic pathological findings in selected organs from infected sheep. Replication was demonstrated in two major cell types: vascular endothelial cells, and agranular leukocytes which morphologically resemble lymphocytes, monocytes/macrophages and/or dendritic cells. Two organs (the skin and tonsils) were shown to support relatively high levels of BTV replication, although they have not previously been proposed as important replication sites during BTV infection. The high level of BTV replication in the skin is thought to be of major significance for the pathogenesis and transmission of BTV (via biting insects) and a refinement of our current model of BTV pathogenesis is discussed.