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

Abstract

The fusion (F) glycoprotein of respiratory syncytial virus (RSV) is synthesized 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 produced 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 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 F 0 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 F 0 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.