Entomopoxviruses (EPVs) are large (300-400 nm) oval-shaped viruses replicating in the cytoplasm of their insect host cells. At the end of their replicative cycle EPVs virions are occluded in a highly expressed protein called spheroidin. This protein forms large (5-20 mm long) oval-shaped occlusion bodies (OBs) called spherules. The infectious cycle of EPVs begins with the ingestion by the insect host of the spherules, their dissolution by the alkaline reducing conditions of the midgut fluid and the release of virions in the midgut lumen. The infective particles first replicate in midgut epithelial cells, then pass the gut barrier to colonise the internal tissues, mainly the fat body cells. Whilst spheroidin has been demonstrated to be non-essential for viral replication, it plays an essential role in the natural biological cycle of the virus in protecting virions from adverse environmental conditions (e.g. UV degradation) and thus improving transmission efficacy. In this respect, spheroidins are functionally similar to polyhedrins of baculoviruses or cypoviruses.