Bluetongue Virus Targets Conventional Dendritic Cells in Skin Lymph

Abstract

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 and then disseminates to secondary organs where it induces edema, hemorrhages, and necrosis. In this study, we show that ovine conventional dendritic cells (cDCs) are the 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 the 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 cDCs 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., interleukin-12 (IL-12), IL-1␤, and IL-6. BTV-infected cDCs stimulated antigen-specific CD4 and CD8 proliferation as well as gamma interferon production. BTV initially targets cDCs while preserving their functional properties, reflecting the optimal adaptation of the virus to its host cells for its first spread.

Virological and pathological findings in Bluetongue virus serotype 8 infected sheep

“…Viremia is highly cell-associated as BTV first replicates in dendritic cells, endothelial cells and mononuclear phagocytes (Barratt-Boyes and MacLachlan, 1994;Hemati et al, 2009). However, during the later stages of viremia, BTV is exclusively associated with the red blood cell fraction which results in a prolonged, but not persistent viremia (Barratt-Boyes and MacLachlan, 1995;Singer et al, 2001).…”

Existence of CD8α-Like Dendritic Cells with a Conserved Functional Specialization and a Common Molecular Signature in Distant Mammalian Species

“…LD lymph cells (25-50% DCs) were obtained after centrifugation on a 1.065 density iodixanol gradient according to procedures described previously by our group (33). They were used either fresh or frozen depending on the number of cells required for the experiments.…”

“…They were used either fresh or frozen depending on the number of cells required for the experiments. LD lymph cells were labeled as previously reported (28,33,34) using anti-ruminant determinant-reacting mAbs, including anti-…”

Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases

“…Culture supernatants were collected and stored at Ϫ80°C. Fifty percent tissue culture infective doses (TCID 50 s) were estimated by endpoint titration on BHK-21 cells (method of Spearman-Karber) by using a previously described protocol (17).…”