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

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.

Transcriptome analysis reveals common differential and global gene expression profiles in bluetongue virus serotype 16 (BTV-16) infected peripheral blood mononuclear cells (PBMCs) in sheep and goats

“…Infected ruminants may exhibit a prolonged viraemia following which the virus could be identified in a number of tissues and organs. BTV replication in agranular leucocytes that are morphologically similar to lymphocytes, monocytes and dendritic cells or macrophages has been confirmed using confocal microscopy [14]. Monocytes infected with BTV in vivo showed cytopathic effect (CPE) after a few days of post-infection, while freshly isolated lymphocytes were resistant to infection [15], [16].…”

Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4

“…One of the mechanisms proposed for lymphoid depletion includes apoptosis 34. Alternatively, BTV replication in lymphocytes, monocytes/macrophages and/or dendritic cells could result in cellular injury 35. Lymphoid depletion could produce immunosupression and predisposition to secondary microbial infections as it has been observed in experimental infections of sheep with BTV.…”

A review of experimental infections with bluetongue virus in the mammalian host

“…The majority of experimental infections with BTV are based on the infection of experimental animals through needle injection. It has quite correctly been pointed out that this is not a natural route of infection and that the extent to which it mimics the natural transmission of the virus by Culicoides midges is not known (Darpel et al, 2012). It is likewise uncertain whether the early development of clinical signs in experimental animals (and by implication pathological lesions) may have been partly due to artificial infection routes.…”