Endoproteolytic activation of Newcastle disease virus fusion proteins requires an intracellular acidic environment.

Effects of weak bases, chloroquine and ammonium chloride, on the intracellular cleavage of the fusion protein precursor (F0) were examined in BHK cells infected with a virulent strain of Newcastle disease virus (NDV). Most of F0 molecules synthesized during a 15-min pulse period were chased out because of cleavage into F1 and F2 within a 60-min chase period in the absence of the weak bases. In contrast, significant amounts of the precursor were found to remain uncleaved when chloroquine or ammonium chloride was present. The uncleaved fusion proteins were incorporated into progeny virions as efficiently as cleaved ones, and about the half of fusion proteins were present as F0 in the virion released by the cells treated with 0.3 mM chloroquine. Taken together with the finding that the trans cisternae of Golgi apparatus and forming secretory vesicles have an acidic pH (K. G. W. Anderson and R. K. Pathak, Cell, 40, 685-643, 1985), the present results suggest that an acidic environment in these compartments is required for intracellular proteolytic activation of NDV fusion proteins.