Cleavage of the respiratory syncytial virus fusion protein is required forits surface expression: role of furin

The fusion (F) glycoprotein of respiratory syncytial virus (RSV) is synthes ized as a nonfusogenic precursor protein (F-0), which during its migration to the cell surface is activated by cleavage into the disulfide-linked F-1 and F-2 subunits. In the present study, soluble secreted human furin produc ed by a recombinant baculovirus cleaved RSV F-0 into proteins the size of F -1 and F-2. Furthermore, cleavage of F-0 was partially inhibited in the fur in defective LoVo cell line, in calcium depleted HEp-2 cells, and in HEp-2 cells treated with the furin inhibitor decanoyl-R-V-K-R-chloromethylketon. These findings strongly suggest an important role for furin in activation o f the RSV F protein. The F-0 protein could not be detected on the surface o f cells, in which F protein activation was inhibited, and RSV particles did not appear to be released from these cells. It thus seems that in contrast to the F proteins of most other paramyxoviruses, the RSV F-0 protein is ve ry inefficient in reaching the cell surface or is unable to reach the cell surface and therefore cannot be incorporated into virus particles. (C) 2000 Published by Elsevier Science B.V. All rights reserved.