On the basis of virus co-localisation with dextran, and the sensitivity to EIPA or actin disruption, the BTV-1 BHK cell entry route appears to be most closely related to macropinocytosis [36] . A number of viruses including vaccinia virus [68, 69, 70] , coxsackievirus B3 [71] , HIV [72] , KSHV [66] , echovirus 11 [73, 74] , human rhinovirus-14 [75] and Adenovirus type 3 [76] have been shown to exploit macropinocytosis, or macropinocytosis-like endocytic pathways for cell-entry and infection. Macropinosomes can deliver their contents to late endosomal compartments (late-endosomes or lysosomes) without the need for early-endosomes [32, 59] . Similarly, the route described here for BTV-1 entry into BHK cells also appears to by-pass early-endosomes and delivers virus to late endosomal compartments. These observations suggest that infection (i.e. acid induced membrane penetration) might occur from within late-endosomes or lysosomes. However, we cannot yet be certain that these compartments are the site of infection as the intermediate steps of virus trafficking between the plasma membrane and late-endosomal compartments are not known, and it is possible that virus could be exposed to a low pH on transit.