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

The fusion (F) glycoprotein of respiratory syncytial virus (RSV) is synthesized as a nonfusogenic precursor protein (F0), which during its migration to the cell surface is activated by cleavage into the disulfide-linked F1 and F2 subunits. In the present study, soluble secreted human furin produced by a recombinant baculovirus cleaved RSV F0 into proteins the size of F1 and F2. Furthermore, cleavage of F0 was partially inhibited in the furin 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 of the RSV F protein. The F0 protein could not be detected on the surface of 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 F0 protein is very inefficient in reaching the cell surface or is unable to reach the cell surface and therefore cannot be incorporated into virus particles.