In conclusion, we have described here a pathway for BTV-1 uptake and infection of BHK cells that is independent of clathrin and cholesterol requires dynamin, appears to deliver virus directly to late-endosomes/lysosomes without first passing through earlyendosomes, and shares characteristics with macropinocytosis. Recently, Forzan et al., [45] reported that BTV-10 infection of Vero and Hela cells is mediated by CME with acid-induced infection occurring within early-endosomes. Hence, BTV joins an increasing number of viruses that appears able to use more than one endocytic pathway to initiate infection [21, 66, 79, 80, 81, 82] . BTV infects a wide variety of cell types in its mammalian hosts including endothelial cells [37] , mononuclear phagocytes [83] , cd T cells [84] , dendritic cells [85] , and a variety of leukocytes [37, 86] . It is likely that this broad tropism, and the ability of BTV to replicate in such evolutionary distant hosts results, in part from an ability to use multiple entry routes to initiate infection. Moreover, BTV can exist in at least three different forms that are all considered to be infectious. These include intact virus particles, infectious sub-viral particles, and virus-cores [46] . These different particle types have different surface components, and may therefore also use different entry mechanisms for infection. However, the entry route used by BTV to infect its natural target cells and the relevance of these pathways to pathogenesis in the animal and insect hosts will require further study. Assessing the human immune system through blood transcriptomics Blood is the pipeline of the immune system. Assessing changes in transcript abundance in blood on a genome-wide scale affords a comprehensive view of the status of the immune system in health and disease. This review summarizes the work that has used this approach to identify therapeutic targets and biomarker signatures in the field of autoimmunity and infectious disease. Recent technological and methodological advances that will carry the blood transcriptome research field forward are also discussed. outgoing lymphatic vessels, the cells again reach the bloodstream to be transported to tissues throughout the body. Upon patrolling these tissues, they gradually drift back into the lymphatic system to re-enter the blood and begin the cycle all over again. Th e complex patterns of recirculation depend on the state of cell activation, the adhesion molecules expressed by immune and endothelial cells, and the presence of chemotactic molecules that selectively attract particular populations of blood cells. Circulating immune cells are, in addition, exposed to factors that are released systemically.