The flavivirus prM/pr protein plays multiple roles in the virus life cycle (reviewed in [26] ). prM acts as a chaperone for E protein folding [37] and associates with the tip of E [34] . prM also appears to respond to low pH to permit E rearrangement on the virus surface and allow furin access for prM processing [34, 38] . Following cleavage, the pr peptide may prevent premature virus fusion through bridging interactions that stabilize the E homodimer and thereby prevent dissociation to E monomers, a key fusion intermediate [35, 36] . To better understand these multiple roles of prM/pr, separation of its chaperone and pH-protection functions and characterization of the pr-E interaction are needed.