Figure 4.

Proposed Model of the Fusion Mechanism of Pestiviruses

A covalently linked E1-E2 heterodimer is present on the viral membrane. E2 binds to the host receptor (possibly CD46, shown in light blue) through domain DB prior to endocytosis. As CD46 is not internalized, a putative secondary receptor (transparent) presumably replaces CD46. Throughout this process the putative fusion loop of E1 (magenta), is concealed by domain DA of E2. At low pH, domain DA of E2 becomes disordered and exposes the fusion loop that will then be able to insert into the endosome membrane and trigger membrane fusion. It is as yet unknown whether E1 forms trimers as seen for other fusion proteins.